FDA Weighs Days of Survival
Is a cancer pill effective if it prolongs life by just 12.8 days?
The Food and Drug Administration is expected to decide today whether to approve Tarceva as a treatment for pancreatic cancer. The companies behind the pill say it offers a real benefit to patients with the terminal disease -- nearly two weeks of life.
But some cancer specialists say the FDA should set the bar for approval higher because there is no evidence Tarceva improves the quality of patients’ lives.
“We don’t know if patients spent the extra week or 10 days in the hospital, or in hospice or on morphine,” Georgetown University cancer specialist Bruce Cheson said.
The agency’s decision is certain to fuel an ongoing debate over the FDA’s procedure for approving cancer drugs. Some critics have complained that the agency has been lax and has cleared ineffective drugs for sale. Others have charged that the FDA has dragged its feet in making cancer drugs available to dying patients.
The case of Tarceva is complicated by the fact that the pill would add $2,000 a month to the cost of treating pancreatic cancer, because it would be taken in addition to existing drugs for the disease. Former Health and Human Services Secretary Tommy G. Thompson, at a news conference in San Francisco last month, said the benefits of Tarceva were meager, given the cost.
“I could be wrong, but in my opinion, Medicare won’t pay for that,” said Thompson, who formerly oversaw the FDA and the Medicare agency, which is charged with implementing a multibillion-dollar prescription drug benefit next year.
But a Medicare spokesman said private insurers offering Medicare prescription drug plans would have the final say on Tarceva -- a decision that could hinge on FDA approval. Sales to patients with pancreatic cancer could total $300 million a year, according to Wall Street estimates.
Tarceva was developed by Genentech Inc. of South San Francisco, Calif., and OSI Pharmaceuticals of Melville, N.Y. The companies already market the pill as a secondary treatment for lung cancer. The drug has posted more than $200 million in sales since its approval as a lung cancer drug a year ago.
The companies said Tarceva added 12.8 days to the median life expectancy of pancreatic cancer patients who took it along with chemotherapy in a clinical trial. Patients taking the two-drug combination had a median survival of 6.2 months compared with 5.9 months for the patients receiving only chemotherapy.
Genentech and OSI said Tarceva was an important step forward in a disease with few treatment options. Although pancreatic cancer accounts for 2% of all new cancer cases in the U.S., it is the fourth leading cause of cancer death. The disease typically is not diagnosed until it has spread beyond the pancreas, a 5-inch gland surrounded by the stomach and the small intestine. Chemotherapy, sometimes in combination with radiation, is the most common treatment for the disease, but it is not very effective.
Gabriel Leung, president of OSI’s oncology unit, said measuring median survival -- the time elapsed before half the patients had died -- understated the benefit of Tarceva because some patients taking Tarceva lived for many months.
In fact, 23% of patients on the Tarceva combination were alive at the end of one year, compared with 17% on chemotherapy alone, he said. “For a patient diagnosed on New Year’s Eve, the chance of seeing the following Christmas has gone up nearly 40%,” Leung said.
An FDA advisory panel made up of outside experts in September recommended approval of Tarceva by a 10-3 vote. Georgetown’s Cheson was one of the dissenters.
However, an analysis prepared by the FDA staff questioned the benefits of Tarceva. The agency found that the pill caused a “significant increase in toxicity,” including a sixfold rise in strokes. The improvement in life expectancy might not be “clinically meaningful,” the FDA report said.
USC cancer specialist Silvana Martino said she was concerned that patients would be attracted to the fact that Tarceva improved survival without taking into account that the drug had potentially harmful side effects and that the added time patients could expect was short.
“The fact that I am living a little bit longer does not mean I am living well,” said Martino, who chaired the FDA panel and voted to reject the drug.
Martino said the “the bigger issue is [determining] when a drug is worthy of being placed on the market,” adding that she was “not impressed when I have to count the survival benefit in days.”
But Julie Fleshman, president of PanCAN, a patient advocacy group, said the additional days were meaningful to patients and that quality of life was difficult to measure. “It is different for every person. For some, it is not feeling pain. For others, it is not losing your hair. For others, it is just being around your loved ones,” she said.
Genentech President Susan Desmond-Hellman, a physician, said the decision about using a drug should be left to patients and their physicians.
“The worst conversation for a physician is telling a patient ‘You have a cancer that can kill you.’ I never got used to that. The second-worst discussion is: ‘We’ve run out of things to try.’ This therapy gives caregivers and patients one more option,” she said.
Tarceva is a “targeted” drug designed to slow down cancer by blocking a protein that spurs tumor growth. Targeted therapies primarily go after cancer cells. Chemotherapy, on the other hand, destroys healthy as well as malignant tissue.
